ROLE OF INTRAFOLLICULAR ACTIVIN AND FOLLISTATIN IN PCOS

该项目的总体目标是调查关键的 抑制素/激活素/卵泡抑素系统的自分泌/旁分泌作用 人正常卵泡发育及多囊卵巢妇女 综合征(PCOS)。以解决导致经典的 PCOS卵巢外观多外周排列，体积小 卵泡，我们假设过多的生物可用激活素 有助于促进卵泡发育以及 成熟卵泡发育停滞。我们的方法是获得 正常或多囊卵巢综合征患者的经阴道卵泡抽吸物 志愿者，然后可以用来记录从一个 激活素B对抑制素A占优势的微环境 通过以前的免疫组织化学方法。具体来说，我们建议： 具体目标1：描述卵泡内的作用 自分泌/旁分泌调节中的抑制素/激活素/卵泡抑素轴 人类正常的卵泡发生和排卵。 特定目标2.抑制素/激活素亚基缺陷的特征 异常卵泡的生物合成、加工或二聚化 在多囊卵巢综合征中观察到成熟。 明确卵泡内卵泡抑素在卵泡发育中的作用 调节激活素活性，从而调节卵泡生长 多囊卵巢综合征。 具体目标4.确定FS调节激活素的机制 人颗粒细胞及相关细胞系在细胞表面的作用 模特们。 因此，本项目努力提供关键信息，以促进 从长凳(具体目标4)过渡到床边(具体目标2和 3)同时还提供有价值的规范性数据库(具体目标1) 用于分析多囊卵巢综合征和其他卵巢病理生理学研究。

The broad goal of this project is to investigate the critical autocrine/paracrine role of the inhibin/activin/follistatin system in normal human follicular development and in women with Polycystic Ovary Syndrome (PCOS). To address the underlying defects leading to the classic PCOS ovarian appearance of numerous peripherally arranged, small follicles, we hypothesize that an excess of bioavailable activin contributes to both increased follicular development as well as developmental arrest of maturing follicles. Our approach is to obtain transvaginal follicular aspirates from well-characterized normal or PCOS volunteers, which can then be used to document the progression from an activin-B dominant to an inhibin-A dominant microenvironment suggested by previous immunohistochemical approaches. Specifically, we propose: Specific Aim 1: To delineate the role of the intrafollicular inhibin/activin/follistatin axis in the autocrine/paracrine regulation of normal folliculogenesis and ovulation in the human. Specific Aim 2. To characterize defects in inhibin/activin subunit biosynthesis, processing or dimerization in the abnormal follicular maturation observed in PCOS. Specific Aim 3. To determine the role of intrafollicular follistatin in regulating activin activity, and thereby follicular growth, in women with PCOS. Specific Aim 4. To determine the mechanism whereby FS regulates activin action at the cell surface in human granulosa cells and related cell line models. Thus, this Project strives to provide key information to facilitate the transition from bench (Specific Aim 4) to bedside (Specific Aims 2 and 3) while also providing a valuable normative database (Specific Aim 1) for analysis of PCOS and other studies of ovarian pathophysiology.